接受HAART治疗的1718例HIV／AIDS患者中医证候研究

目的：通过调查接受HAART治疗的HIV／AIDS患者的症状分布规律,探讨该类患者的中医证候特点。方法：选取接受HAART治疗3个月以上的HIV／AIDS患者1718例进行横断面调查,采集中医四诊信息和现代生物学信息,对这些患者进行症状、体征、证候出现频率（次）的描述性统计。结果：常见症状依次为：乏力、纳呆、咳嗽、头痛、月经失常（女性）、关节痛、皮肤瘙痒、腰痛、肌肉痛、发热;舌色以红、绛红、淡白及紫色为主,舌形以薄舌、胖大舌、齿痕舌为主,舌苔则以薄白苔和黄腻、厚腻苔多见;脉象以复合脉象为主,分解后脉象以细脉、滑脉、弦脉最为多见。共出现中医证型24种,气血两亏、气阴两虚是最常见的证型,其次为痰热内扰证、肝郁气滞火旺证、脾肾亏虚及湿邪阻滞证。多为复合证型,分解后出现的单证达32种。单证以虚证为主,其次为实证,虚实夹杂最少。脏腑的发病率由高至低依次为脾、肺、肾、肝、心,其中脾系发病率最高,且常与肺、肝、肾合而为病。发病脏腑数目由高至低依次为：三脏同病、二脏同病、四脏同病、一脏发病、五脏同病。结论：接受HAART治疗的HIV／AIDS患者临床症状体征表现多样,病情复杂,证候多见虚实夹杂,以虚为主,涉及脏腑主要为脾、肺、肾,常见多脏腑同病。     

Utilizing an Ingestible Biosensor to Assess Real-Time Medication Adherence

Medication adherence monitoring has relied largely on indirect measures of pill ingestion including patient self-report, pharmacy refills, electronically triggered pill bottles, and pill counts. Our objective is to describe an ingestible biosensor system comprising a radio-frequency identification (RFID)-tagged gelatin capsule. Once the capsule dissolves in the stomach, the RFID tag activates to transmit a unique signal to a relay device which transmits a time-stamped message to a cloud-based server that functions as a direct measure of medication adherence. We describe a constellation of mobile technologies that provide real-time direct measures of medication adherence. Optimizing connectivity, relay design, and interactivity with users are important in obtaining maximal acceptability. Potential concerns including gut retention of metallic components of the ingestible biosensor and drug dissolution within a gelatin capsule should be considered. An ingestible biosensor incorporated into a medication management system has the potential to improve medication compliance with real-time monitoring of ingestion and prompt early behavioral intervention. Integration of ingestible biosensors for multiple disease states may provide toxicologists with salient data early in the care of poisoned patients in the future. Further research on device design and interventions to improve adherence is needed and will shape the evolving world of medication adherence.     

STRUCTURED THERAPY INTERRUPTION (STI) AND DECEPTIVE IMPRINTING

The immune response in individuals chronically infected with HIV-1 is unable to prevent progression of disease. Diversion of immune recognition via ‘Deceptive Imprinting’ allows virus variants to continue the infection. Stuctured Interrupting of (HAART) therapy (STI) causes rebound of virus with ‘wild-type’ strains that stimulate the immune system. Combining STI with suppression of the dominant response against anti-wild–type virus is proposed to enhance the beneficial effects of STI.     

Optimal timing for initiation of highly active antiretroviral therapy in treatment-naïve human immunodeficiency virus-1-infected individuals presenting with AIDS-defining diseases: the experience of the PISCIS Cohort

In this prospective, multicentre cohort study, we analysed specific prognostic factors and the impact of timing of highly active antiretroviral therapy (HAART) on disease progression and death among 625 human immunodeficiency virus (HIV)-1-infected, treatment-naïve patients diagnosed with an AIDS-defining disease. HAART was classified as early (<30 days) or late (30–270 days). Deferring HAART was significantly associated with faster progression to a new AIDS-defining event/death overall (p 0.009) and in patients with Pneumocystis jiroveci pneumonia (p 0.017). In the multivariate analysis, deferring HAART was associated with a higher risk of a new AIDS-defining event/death (p 0.002; hazard ratio 1.83; 95% CI 1.25–2.68). Other independent risk factors for poorer outcome were baseline diagnosis of AIDS-defining lymphoma, age >35 years, and low CD4⁺ count (<50 cells/μL).     

Factors associated with the failure of HIV-positive persons to return for scheduled medical visits

Abstract

PURPOSE: To assess in an HIV-positive cohort the cumulative probability of failing to return for scheduled medical visits and to address the factors associated with follow-up discontinuation. METHOD: This was a hospital-based cohort study conducted from January 1985 through September 1999. Out of 3,300 HIV-1 infected patients, 1,680 patients with CD4 count <500 cells/mL or with AIDS diagnosis were included in the analysis because they received scheduled medical visits for follow-up at our center. Baseline visit was the first visit when patients met the criteria for enrollment. The main outcome measure was failure to return for scheduled medical visits for at least 12 consecutive months. RESULTS: The probability of returning decreased rapidly in the first months after the baseline visit. After 1 year since enrollment, 25% of patients failed to return and after 2 years 34% of patients failed to return. Most patients who failed to return for visits (78%) discontinued their follow-up within 6 months since enrollment. In multivariate analysis, patients in the intravenous drug use (IDU) category were most likely to fail to return for scheduled appointments, as were patients with higher CD4 count (CD4 >50 cells/μL) or patients without AIDS diagnosis. Patients with shorter follow-up had a higher risk of failing to return (odds ratio [OR]: 0.12, 0.36, 0.45, and 0.74 for >36, 24-36, 12-24, and 6-12 months of follow-up respectively vs. <6 months). Patients who were enrolled in more recent years had a higher compliance to follow-up visits (OR: 0.33, 0.63, and 0.61 for ≥1997, 1995-1996, and 1988-1994 vs. <1988). CONCLUSION: Patients in the IDU category, patients without AIDS diagnosis, or patients with higher CD4 counts are more likely to miss medical appointments and discontinue their follow-up. More recently enrolled patients have a lower risk of failing to return. It is possible that the recent and more effective anti-HIV treatment played a major role in increasing adherence to follow-up.     

Treatment Durability,Effectiveness, and Safety with Atazanavir/Ritonavir-Based HAART Regimen in Treatment-Naïve HIV-lnfected Patients

Abstract

Purpose: To describe the durability of treatment, virological and immunologi-cal response, and safety of an atazanavir/ritonavir (ATV/RTV)-based highly active antiretroviral therapy (HAART) regimen in treatment-naïve HIV-infected patients. Methods: This was a multicentre retrospective study. Medical charts of antiret-roviral-na’i’ve HIV-infected adults who initiated ATV/RTV (300/100 mg) from January 2004 to December 2007 in 10 Canadian clinics were reviewed. Data were collected from time of ATV/RTV treatment initiation until discontinuation of ATV. Durability of treatment and time to virological response were estimated with Kaplan-Meier functions. Change in viral load, CD4 cell counts, and lipid parameters were assessed with linear regression analyses. Results: 176 patients were enrolled, 153 (86.9%) were male, and the majority (52.3%) were 40 to 54 years old. Duration of observation ranged from 1.6 to 56 months. The mean (S£) durability of treatment was 33.5 (0.7) months. There were 37 (21.0%) patients who discontinued ATV/ RTV, among whom 18 (10.2%) discontinued due to toxicity, suboptimal virological response, loss to follow-up, or death. The mean (S£) time to HIV viral load of <50 and <400 copies/mL was 6.6 (0.4) and 4.3 (0.3) months, respectively. At 96 weeks of treatment, least squares mean (LSM) estimated change in log₁₀(HIV copies/mL) was -2.94 (P < .001) and +245 cells/mL (P < .001) for CD4 cell count. A significant LSM increase in HDL-C of 0.24 mmol/L (P = .007 for trend over time) was also observed; total cholesterol, triglycerides, and LDL-C increased over time but their change did not reach statistical significance. The most frequently reported adverse event was increased bilirubin (16.5%). Conclusions: ATV/RTV-based first-line HAART regimen demonstrated durability and effectiveness and was well tolerated in treatment-naïve HIV-infected patients.     

TTV Viral Load As a Marker for Immune Reconstitution After Initiation of HAART in HIV-Infected Patients

Abstract

Purpose: To investigate whether TT virus (TTV) viral load may be used as a surrogate marker for functional immune reconstitution in HIV-infected patients receiving highly active antiretroviral therapy (HAART). Method: Fifteen protease inhibitor-naÏve HIV-infected patients were included in a longitudinal study. From each patient, three serum samples taken before HAART initiation and three samples taken during HAART were analyzed. TTV was detected by polymerase chain reaction (PCR) and was quantitated by competitive PCR. TTV viral heterogeneity was determined by restriction fragment length polymorphisms (RFLPs) and sequencing. Results: All 15 HIV-infected patients were TTV positive. No significant change in HIV RNA or TTV viral load was observed at the three time points before HAART initiation. Even though HAART lead to an immediate and significant reduction in HIV RNA (p = .0001), a significant reduction in TTV viral load (p = .0002) was not observed until after 3-5 months of HAART. Four patients did not have an increase in CD4+ T cell count after 1 year of HAART; however, a decrease in TTV viral load was still observed, and three of these patients had a reduction in HIV RNA. RFLPs and sequencing revealed that TTV is represented as a heterogeneous population of virus in HIV-infected patients. Conclusion: This pilot study suggests that HAART leads to improved immunological responses, even in patients who do not have an increase in CD4+ T cell counts. We propose that the change in TTV viral load may be useful in the evaluation of cellular immune response at a functional level in HIV-infected patients who receive HAART.     

Comparison of Prognostic Importance of Latest CD4+ Cell Count and HIV RNA Levels in Patients with Advanced HIV Infection on Highly Active Antiretroviral Therapy

Abstract

The comparative prognostic importance of latest plasma HIV RNA levels (viral loads) and CD4+ cell counts among patients prescribed highly active antiretroviral therapy (HAART) has not been well characterized. Method: We assessed the prognostic value of latest CD4+ cell counts and latest viral loads for progression to AIDS or death and explored their interaction among 432 HIV-infected persons with advanced HIV who were prescribed a protease inhibitor (PI) as their first HAART regimen. Results: Pre-HAART median CD4+ cell count and viral load were 41 cells/mm³ and 126,331 copies/mL, respectively. After 12 months of HAART, the median CD4+ cell count was 154 cells/mm³; 39% of patients had a viral load of 400 copies/mL or lower. Over a median follow-up of 33 months, 109 (25%) of the 432 patients experienced an AIDS event or died. The hazard ratio for AIDS or death for those with latest CD4+ cell count <50 cells/mm³ versus ≥200 cells/mm³ was 13.9 (95% CI 6.5 to 29.7) without adjustment for latest viral load measurements and 9.5 (95% CI 4.0 to 22.5) after adjustment for latest viral load. In contrast, the hazard ratio for AIDS or death for those with viral load ≥100,000 versus <400 copies/mL was 4.2 (95% CI 2.3 to 7.7) without adjustment for latest CD4+ level and 1.2 (95% CI 0.6 to 2.4) with adjustment for latest CD4+ cell count. Conclusion: We conclude that when latest CD4+ cell count and viral load are considered separately, both are significantly related to AIDS or death; when these markers are jointly considered, the association of viral load with AIDS or death is substantially diminished. Latest CD4+ levels are more strongly related to AIDS or death than latest viral load levels in patients on HAART.     

Predictors of AIDS-Defining Events Among Advanced Naïve Patients After HAART

Abstract

Background: Baseline and follow–up predictors of new AIDS-defining events or death (ADE/death) among patients who started HAART late in their disease history have rarely been assessed simultaneously. Method: ADE and mortality rates were assessed using Cox regression analyses. Variables were tested for prediction of ADE/death within the first 3 months of therapy and from month 3, thereafter. Results: 751 HIV–infected patients with <200 CD4+/mm³ before HAART were followed for a median of 49 months. 207 new ADE occurred (7.06 [6.16–8.10] per 100 patient-years). ADE/deaths clustered within the first 3 months of treatment (106/207, 51%). Higher CD4+ T-cell counts during the follow–up (per log_e cells/mm³: hazard ratio [HR] 0.51; 0.41–0.64; p < .001) and use of antiretroviral therapy (HR 0.38; 95% CI 0.21–0.69; p = .001) appeared to protect from ADE/death after month 3. Conversely, increasing follow–up with HIV RNA >400 copies/mL correlated with ADE/death (per month: HR 1.09; 95% CI 1.06-1.12; p = .001). Use of boosted protease inhibitors as first-line HAART and HCV-seropositivity were additional risk factors. Baseline CD4+ T-cell count and HIV RNA had a predominant impact in the first 3 months after HAART initiation. Conclusion: A careful monitoring of patients with low CD4+ is particularly necessary during the first few months of HAART. Length and extent of viral replication during the follow-up appeared to induce a significantly higher risk of HIV disease progression afterwards, implying that new drugs and new strategies aimed at ensuring long-term suppression of HIV RNA are of outstanding importance.